Aim: The objective of this study is to compare the efficacy of different recombinant, commercially available WNTs with regard to WNT/β-catenin signaling, Dishevelled (DVL) and G protein activation and the induction of cell proliferation in a microglia-like cell line called N13. Method: For detection of activated signaling molecules, cell lysates are analysed by immunoblotting. Further, we use a [γ(35) S]GTP binding assay to monitor the exchange of GDP for GTP in heterotrimeric G proteins in N13 membrane preparations. Cell proliferation was assessed by the MTT assay measuring mitochondrial function, which is proportional to the amount of viable cells. Results: Of the WNTs tested (WNT-3A, -4, -5A, -5B, -7A, 9B), only WNT-3A activated WNT/β-catenin signaling in N13 cells. All WNTs induced the formation of phosphorylated and shifted DVL and the activation of heterotrimeric G proteins with variable efficacies. WNT-5A and WNT-9B, which had the highest efficacy in the G protein assay also induced N13 cell proliferation. Conclusions: WNTs show significant differences in their efficacy to activate β-catenin-dependent and -independent signaling. The WNTs tested are present during maturation of the central nervous system and/or in the adult brain and are thus potential regulators of microglia-mediated neuroinflammation.